CN116547374A - Control unit for a fluid control device - Google Patents

Control unit for a fluid control device Download PDF

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Publication number
CN116547374A
CN116547374A CN202180079176.9A CN202180079176A CN116547374A CN 116547374 A CN116547374 A CN 116547374A CN 202180079176 A CN202180079176 A CN 202180079176A CN 116547374 A CN116547374 A CN 116547374A
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Prior art keywords
control unit
processing device
fluid
pressure
gas tank
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CN202180079176.9A
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Chinese (zh)
Inventor
蔡承翰
官大涵
江承昱
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Shengdenai Biotechnology Co ltd
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Shengdenai Biotechnology Co ltd
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Publication of CN116547374A publication Critical patent/CN116547374A/en
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L1/00Enclosures; Chambers
    • B01L1/02Air-pressure chambers; Air-locks therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/14Pressurized fluid
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
    • G01N21/80Indicating pH value
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/028Modular arrangements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0681Filter
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N2021/178Methods for obtaining spatial resolution of the property being measured

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
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  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Clinical Laboratory Science (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Sustainable Development (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Plasma & Fusion (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

The present invention relates to a control unit for a fluid control device, wherein the control unit comprises a pressure unit for providing a positive and/or negative pressure; at least one first control unit outlet fluidly connectable to a processing device comprising at least one container for receiving a fluid sample; at least one second control unit outlet fluidly connectable to a processing device having a chamber for receiving the processing device; and a connection unit through which the pressure unit is fluidly connectable or fluidly connected to the first control unit outlet and/or the second control unit outlet, wherein the control unit is adapted to control the processing of the fluid sample in the processing device by applying positive or negative pressure provided by the pressure unit to the first control unit outlet by the connection unit and to control a physical state in a chamber of the processing device.

Description

Control unit for a fluid control device
Technical Field
The present invention relates to a control unit for a fluid control device and a fluid control device including the control unit.
Background
In the pharmaceutical process of bio-similarity drugs, most biopharmaceuticals require cell line development processes. Cell line development is a method of screening proteins/antibodies, achieving high yields of proteins/antibodies, and optimizing their quality. However, on the other hand, cell line development is a fairly complex, labor intensive and expensive process. Most pharmaceutical factories are developed for half a year.
The central tool required in cell line development is a bioreactor for cell culture. The process starts with the cultivation of single cells, and the scale is continuously enlarged to the mass production scale by repeating the screening and enlarging transfer steps. Thus, for different stages and different amounts of cells, different sizes of bioreactors are required, from micro-liter scale bioreactors to large scale bioreactors of high volume production scale. However, there are limitations to optimizing the cell culture environment of smaller size bioreactors. Ideal bioreactors generally require continuous growth of cells in suspension, dynamic monitoring of biological signals, and feedback control of dissolved oxygen and pH. It is difficult to achieve the above functions in micro-liter-scale bioreactors.
The traditional method in cell culture equipment is to place cells in culture well plates (96-well plates and 24-well plates) of different sizes for static culture. In this way, however, the cells will settle to the bottom of the well plate. As a result, cells grow in an inappropriate environment. The disadvantages of static culture are as follows: 1. the growth environment of cells is limited by the 2D space; 2. oxygen dissolves into the culture solution from the upper gas-liquid interface and there is a distance between the cells and oxygen; 3. cellular metabolites accumulate continuously around cells, and so on.
In bioreactors, there are many ways in which a culture environment of a homogeneous mixture can be achieved. Stirring or shaking is the most common way to achieve the effect of a homogeneous mixture. However, since the amount of liquid in 96-well and 24-well plates is too small (reynolds number) it is very difficult to achieve the effect of a homogeneous mixture in a conventional manner. Thus, for 96-well and 24-well dish cell cultures, only static cultures, at most in a shaking manner, can be selected to achieve part of the mixture effect.
For most existing bioreactors, a rapid shaking mode is used to achieve the effect of the fluid mixture. However, this approach can achieve the effect of homogeneous mixtures only in 48-well and 24-well trays, and experiments with homogeneous mixtures have not been successfully performed in 96-well trays. The reason for this is that the amount of liquid in the 96-well plate is too small and the reynolds number is relatively small. Therefore, a rapid shaking speed of more than 1000rpm is required to achieve the mixture effect. In addition, it is difficult to integrate the optical sensors during rapid shaking with such a speed. Detection of the optical signal is not possible during the rapid shake. This is why the orifice disc of existing bioreactors can only have up to 48 orifices.
WO2018/189398A1 discloses a bioreactor comprising a control unit, a well for receiving a fluid sample containing biological particles, and a lid. Since the above-described components are arranged one above the other, the bioreactor has a stacked configuration. The bioreactor has disadvantages in that it has a complicated structure and a low operation flux for culturing samples.
Disclosure of Invention
It is therefore an object of the present invention to provide a control unit which avoids the above-mentioned disadvantages.
This object is solved by a control unit for a fluid control device, wherein the control unit comprises: a pressure unit for providing positive and/or negative pressure; at least one first control unit outlet fluidly connectable to a processing device comprising at least one container for receiving a fluid sample; at least one second control unit outlet fluidly connectable to a processing device having a chamber for receiving the processing device; and a connection unit through which the pressure unit is fluidly connectable or fluidly connected to the first control unit outlet and/or the second control unit outlet, wherein the control unit is adapted to control the processing of the fluid sample in the processing device by applying positive or negative pressure provided by the pressure unit to the first control unit outlet by the connection unit and to control a physical state in a chamber of the processing device.
The control unit according to the invention has the following recognized advantages: the control unit and the processing device may be separated from each other, thereby simplifying the structure of the processing device. In addition, it is recognized that the same control unit can be used for two functions, namely controlling the machining in the machining device and controlling the physical state in the processing device. It has been recognized that, contrary to the known embodiments, the control unit is not only used for controlling the processing of a fluid sample arranged in a processing device but also for controlling the physical state in a chamber of a processing device in which the processing device is arranged. In particular, when the processing device is disposed within a chamber of the processing device, the environment of the processing device may be controlled by the control unit. Thus, the yield of the biological particles in culture is improved.
The processing device and the processing device are not part of the control unit. The processing device may be disposed within a chamber of the processing device. The processing device may be any kind of device that can be used to process a fluid sample. In particular, the processing device may be a device that may be used to supply or remove fluid into a container of the processing device to move and/or mix fluid samples arranged in the container. Such devices may include a lid and a container, and are described in more detail below. Alternatively, the processing device may be any kind of microfluidic device on which a force has to be applied to process a liquid within the microfluidic device. The microfluidic device may be a microfluidic chip.
The fluid sample is dependent on the fluid control device. If the fluid control device is associated with a bioreactor, the fluid sample contains biological particles. The biological particles may be cells or microorganisms. The fluid sample may comprise a liquid and at least one biological particle. The liquid may promote the growth of biological particles (in particular cells or microorganisms) disposed in the liquid.
If the fluid control device is associated with a chemical reactor, the liquid sample may contain one or more chemical reagents. However, if the fluid control device includes a microfluidic device as a processing device, the fluid sample depends on the field of use of the microfluidic device.
The physical state in the chamber may be at least one physical parameter of the chamber, such as the chamber temperature or the chamber pressure or the gas humidity within the chamber or the gas composition within the chamber.
As previously described, processing of the fluid sample may include supplying or removing fluid (particularly gas) to or from a container of the processing device and/or mixing the fluid sample and/or moving the fluid sample and/or agitating biological particles of the fluid sample. Mixing fluid samples is understood to be a process of moving the components of the fluid samples relative to each other in a manner that creates a new configuration. The processing device may perform at least one of the preceding processing steps and/or be controlled by applying positive or negative pressure to the first control unit outlet.
The control unit may be adapted to selectively apply positive or negative pressure to the first control unit outlet. Positive or negative pressure may be alternately applied to the first control unit outlet. Additionally or alternatively, a negative or positive pressure may be applied to the first control unit outlet multiple times. By applying positive or negative pressure to the first control unit outlet in the manner described above, it is ensured that the fluid sample located in the processing unit is processed, in particular mixed.
When fluid can flow from one component to another (or vice versa), there is a fluid connection between the two components.
The connection unit is a unit for fluidly connecting or connectable to the pressure unit to the first control unit outlet and/or to the second control unit outlet.
The first control unit outlet is the outlet through which fluid, in particular gas, exits the control unit or enters the control unit. Likewise, the second control unit outlet is the outlet through which fluid (in particular gas) leaves the control unit or enters the control unit. The first control unit outlet may be part of a first tube in which a fluid, in particular a gas, flows. Alternatively, the first control unit outlet may be part of a first connector that may be used to establish a fluid connection with the processing device. The second control unit outlet may be part of a second tube in which a fluid, in particular a gas, flows. Alternatively, the second control unit outlet may be part of a second connector that may be used to establish a fluid connection with the processing device.
According to an embodiment, the control unit may be adapted to control the physical state in the chamber of the processing device by fluidly connecting or disconnecting the pressure unit with the second control unit by means of the connection unit.
The pressure unit may comprise a pressurized gas tank having a positive pressure, wherein the pressurized gas tank may be fluidly connected to the first control unit outlet and/or the second control unit outlet. When the pressurized gas tank is fluidly connected to the first control unit and/or the second control unit, gas flows from the pressurized gas tank to the first control unit outlet and/or the second control unit outlet.
Additionally or alternatively, the pressure unit may comprise a vacuum gas box having a negative pressure, wherein the vacuum gas box may be fluidly connected to the first control unit outlet and/or the second control unit outlet. When the first control unit outlet and/or the second control unit outlet are fluidly connected to the vacuum gas box, gas flows from the first control unit outlet and/or the second control unit outlet to the vacuum gas box. The positive pressure gas is a gas having a pressure higher than the atmospheric pressure. The negative pressure gas is a gas having a pressure lower than the atmospheric pressure.
Furthermore, the pressure unit may comprise a gas mixer arranged upstream of the pressurized gas tank. The gas mixer is used for mixing at least two gases. In turn, the gas mixer may comprise at least two inlets for the entry of gas. Ambient air or oxygen may be added to the gas mixer via an inlet. Carbon dioxide may be added to the gas mixer via another inlet. Alternatively, other gases may be added to the gas mixer through at least one inlet. The gas mixer may comprise an outlet for releasing the mixed gas.
The pressure unit may comprise a pump arranged upstream of the pressurized gas tank and/or adapted to increase the pressure in the pressurized gas tank. The pump may be disposed downstream of the gas mixer. By providing a pump, it is ensured in a simple manner that the pressure in the pressurized gas tank has a predetermined pressure. In addition, a gas filter may be provided upstream of the pressurized gas tank for filtering the gas. Thus, for example, the supply of dust particles to the processing device and the processing device via the first control unit outlet and/or the second control unit outlet may be avoided.
Furthermore, the pressure unit may comprise a further pump arranged downstream of the vacuum gas tank and/or adapted to reduce the pressure in the vacuum gas tank. By providing the further pump, the vacuum air tank is provided with a predetermined air pressure. The pressure unit has a gas outlet through which gas pumped by the further pump leaves the pressure unit. In particular, the gas outlet is arranged such that the gas pumped by the further pump is expelled into the environment. Another gas filter may be provided downstream of the vacuum gas box.
The pressure unit may comprise a check valve. A check valve may be fluidly disposed between the pressurized gas tank and the first control unit outlet and/or the second control unit outlet. This ensures that only a gas flow from the pressurized gas tank to the first control unit outlet and/or the second control unit outlet occurs. In addition, it is ensured that no gas can flow from the processing device to the pressurized gas tank and/or from the processing device to the pressurized gas tank.
The control unit may supply the same gas to the processing device and the processing device. In particular, when the first control unit outlet and the second control unit outlet are fluidly connected to a pressurized gas tank, the pressurized gas tank may supply the same gas to the processing device and the processing device. Since the gas stored in the pressurized gas tank may be a gas mixture for providing culture support for the biological particles located in the processing device, in embodiments in which the fluid control device is associated with a bioreactor, supplying the gas mixture to the processing device and the processing device may increase the yield of the culture of the biological particles.
According to an embodiment, the connection unit may comprise at least one valve for selectively fluidly connecting the pressurized air tank or the vacuum air tank with the first control unit outlet. This means that the valve ensures that the pressurized air tank or the vacuum air tank is in fluid connection with the first control unit outlet. The valve may be disposed downstream of the pressurized gas tank.
In addition, the connection unit comprises at least one further valve which, in a first position, fluidly connects the pressurized gas tank with, in particular, the second control unit outlet (and thus with the processing device), and, in a second position, separates the fluid connection between the pressurized gas tank and, in particular, the second control unit outlet (and thus with the processing device).
The control unit may comprise at least one controller for controlling the valve and/or the further valve. The controller may thus control whether the first control unit outlet (and thus the processing device) is connected to the pressurized gas tank or to the vacuum gas tank. In addition, the controller may control whether the pressurized gas tank is fluidly connected to the second control unit outlet (and thus to the processing device). The control may be based on sensor signals determined from one or more sensors. The sensor may detect at least one physical state in a chamber of the processing device and/or at least one physical state of the processing device.
In particular, the controller may control the valve based on the flow of gas through the outlet of the first control unit. In this regard, the controller may control the opening degree of the outlet of the valve based on the flow rate of the gas flowing through the outlet of the first control unit. This means that the valve is not only adapted to be in fluid connection with the first and/or second control unit outlet, but it is also capable of controlling the flow of gas through the valve.
Additionally or alternatively, the controller may control the valve based on a physical state in the chamber of the processing device (particularly pressure) and based on a physical state of the processing device (particularly pressure within the processing device). The physical state of the processing device and the physical state of the processing device may be detected by a sensor.
Finally, the controller may control whether the valve connects the first control unit outlet to the pressurized gas tank or to the vacuum gas tank based on a physical state in the chamber of the processing apparatus and based on a physical state of the processing apparatus. This means that at least two physical states can be used to control the valve.
As previously described, the controller may control another valve. In particular, the controller may control the further valve based on a physical state of a chamber of the processing device. The physical state may be a composition of gas within the chamber. Alternatively and/or additionally, the controller may control the further valve based on a physical state of the processing device, in particular a physical state of a fluid sample located in the processing device.
The controller controls the gas mixer based on the physical state of the chamber of the processing device (in particular the gas composition) and/or the physical state of the fluid sample in the processing device. When the processing device is in fluid connection with the processing device, changes in the physical state in the chamber of the processing device (in particular the gas composition in the chamber) have a positive influence on the yield of the biological particle culture.
Information about a fluid sample located in a processing device may be acquired by an acquisition unit. The acquisition unit may comprise an optical imaging device, such as a camera, which takes images of the processing means. In addition, the acquisition unit may determine a physical state of the fluid sample located in the processing device based on the acquired information. The controller may control the gas mixer and/or the further valve based on the determined physical state of the fluid sample. The physical state may be the pH of the liquid sample and/or the oxygen content of the liquid sample.
In addition, the controller is adapted to control a humidifier disposed in the processing device. Thus, the controller may control the physical state in the chamber, in particular the gas humidity, by controlling humidification.
All of the aforementioned control tasks may be performed by the same controller. Alternatively, at least some of the tasks may be performed by sub-controllers. In particular, the controller may comprise a first sub-controller for controlling whether the valve connects the first control unit outlet with the pressurized gas tank or with the vacuum gas tank and/or a second sub-controller for controlling the opening of the valve outlet opening. Additionally or alternatively, the controller may comprise a third sub-controller for controlling another valve and/or the gas mixer and/or a fourth sub-controller for controlling the humidifier. The controller or sub-controller may receive the sensor signal as an input signal.
According to an embodiment, the control unit may comprise a housing. The housing may be provided around an inner space provided with a pressurized gas tank and/or a vacuum gas tank and/or a pump and/or another pump and/or a gas mixer and/or a valve and/or another valve and/or a check valve. Thus, the pressure unit and the connection unit are disposed within the housing. This results in a compact control unit comprising all necessary components for controlling the processing means and the processing unit.
The housing may have at least one through-hole for receiving a fluid connector of the processing device and/or another through-hole for receiving another fluid connector of the processing device. In this case, the fluid connector is connected with a tube of the control unit so that gas can flow from the control unit to the treatment device and vice versa. The further fluid connector is connected with a further tube of the control unit so that gas can flow from the control unit to the processing device and vice versa. The housing may be mechanically coupled to the processing device. The mechanical and/or fluid connection may be in a releasable manner. Additionally, the housing may include an outlet disposed downstream of and fluidly connected to the other pump. Additionally, the housing may include at least two inlets disposed upstream of and in fluid communication with the gas mixer.
All of the foregoing components may be fluidly connected to one another by tubing.
As previously mentioned, the control unit is adapted to control at least one physical state in the chamber of the processing device and to control the processing of the fluid sample in the processing device. However, the same control unit may also be used to control a plurality of processing devices and processing devices. This is done by the control unit applying positive or negative pressure provided by the pressure unit to each of the first control unit outlets by means of the connection unit. The respective first control unit outlets differ from each other in the applied pressure. In addition, the control unit may control physical states in each chamber of each processing apparatus. The control unit may be adapted to cause different physical states to be controlled and/or to cause the physical states in the chambers of the respective processing means to differ from each other. Thus, it is no longer necessary to provide a control unit for each processing device, but rather the same (in particular only one) control unit can be used for controlling a plurality of processing devices and processing devices.
The control unit may comprise only one pressure unit and/or several connection units. The number of connection units may correspond to the number of processing devices and/or machining devices that can be fluidly connected to the control unit. Each of the connection units may include the same components and may have the structure as described above. The pressure units may comprise the same components and have the same structure as described previously.
In a particular embodiment, the control unit may include a plurality of first control unit outlets and a plurality of second control unit outlets. Each of the plurality of first control unit outlets may be fluidly connected to one of the processing devices. In addition, each of the plurality of second control unit outlets may be fluidly connected to one of the processing devices. Each of the plurality of first control unit outlets is independent of the other first control unit outlets. Thus, the gas flow may occur via one or more first control unit outlets. Each of the plurality of second control unit outlets is independent of the other second control unit outlets. Thus, the gas flow may occur via one or more second control unit outlets.
The same pressurized gas tank may be connected to each of the plurality of first control unit outlets and/or each of the plurality of second control unit outlets. Additionally or alternatively, the same vacuum gas box may be connected to each of the plurality of first control unit outlets.
As previously mentioned, the control unit may comprise a plurality of connection units such that the control unit may comprise a plurality of valves. Each valve is in fluid connection with one of the plurality of first control unit outlets, with the pressurized air tank and with the vacuum air tank. Each valve is in fluid connection with one of the plurality of second control unit outlets and with the pressurized gas tank.
In embodiments where the control unit may be fluidly connected to a plurality of processing and/or processing devices, the control unit may include one or more controllers. If the control unit comprises one controller, the controller controls the physical state in all processing means and the processing of the liquid sample in all processing means. Alternatively, the control unit may comprise several controllers. In particular, the number of controllers may correspond to the number of connection units. The controllers may each have sub-controllers as described above.
The pressure unit may have a tube enabling fluid connection of the pressure unit with the treatment device and/or the processing device.
In a particularly advantageous embodiment, a fluid control device is provided. The fluid control device comprises the control unit, at least one processing device and at least one processing device arranged in a chamber of the processing device. The processing device is in fluid connection with the first control unit outlet and the processing device is in fluid connection with the second control unit outlet.
The fluid control device may be associated with a bioreactor. In such embodiments, one or more containers of the processing device may be in the microliter scale. Alternatively, one or more of the containers may be of a greater magnitude.
An advantageous fluid control device is achieved if the fluid control device comprises several processing devices, wherein processing devices may be arranged in the chambers of the respective processing devices. Such a fluid control device has the following advantages: since the same control unit can be used for different processing and/or machining devices, it is compact.
The processing device may include at least one container for receiving a fluid sample and a cover covering the container. The cap may comprise at least one extension tube extending into the container and being fluidly connectable to the first control unit outlet. The cap may include an interior space fluidly connected to the first control unit outlet and the container. The processing device may have a plurality of containers. In particular, the processing device may comprise a porous disc. In this case, the cover may have more than one extension tube. In particular, the cover may be formed such that at least one extension tube extends in each container.
The controller may control the valve such that a positive pressure provided by the pressurized gas tank is applied into the container via the lid or a negative pressure provided by the vacuum gas tank is applied into the container via the lid. By applying such pressure, the fluid sample may be drawn into or dispensed from the extension tube.
The controller controls the other valve such that a predetermined physical state is achieved in the chamber of the processing device. The predetermined physical state may be a composition of gas within the chamber. In addition, the controller may control the humidifier such that the gas in the chamber has a predetermined humidity.
The processing device may comprise a heating unit for heating the processing device and/or heating the chamber of the processing device. The controller may control the physical state in the chamber, i.e. by controlling the heating unit to increase the chamber temperature. Alternatively, the controller may control the heating unit to increase the temperature of the liquid sample located in the processing unit.
The processing device may comprise a housing surrounding a chamber in which the processing device is disposed. Thus, the processing apparatus has a simple structure. The processing device includes a transparent housing portion that enables the acquisition unit to acquire information about a fluid sample located in the processing device.
Drawings
In the drawings, the subject matter of the present invention is schematically illustrated, with elements of the same or similar function generally having the same reference numerals.
Fig. 1 (a) is an exploded view of the processing apparatus.
Fig. 1 (B) is a schematic cross-sectional view of the processing apparatus.
Fig. 2 is a system schematic diagram of a fluid control device according to a first embodiment of the present invention.
Fig. 3 is a flow chart of the manner of operation of the fluid control device according to the first embodiment of the present invention.
Fig. 4 is a system schematic diagram of a fluid control device according to a second embodiment of the present invention.
Fig. 5 is a flow chart of the manner of operation of the fluid control device according to the second embodiment of the present invention.
Fig. 6 is a system schematic diagram of a fluid control device according to a third embodiment of the present invention.
Fig. 7 is a flowchart of an operation mode of the fluid control device according to the third embodiment of the present invention.
Fig. 8 is a perspective view of a treatment device.
Fig. 9 is a perspective view of a portion of a control unit used in the fluid control device according to the present invention.
Fig. 10 is a perspective view of a fluid control device according to the present invention.
Detailed Description
Fig. 1 (a) and 1 (B) each show a processing apparatus. The processing apparatus includes a porous disc 12 having a plurality of receptacles 20. The embodiment shown in the figures has 96 containers. A fluid sample 26 is located in each container 20, wherein the fluid sample 26 comprises a liquid 6 and a plurality of biological particles 5, e.g. cells. The porous disc 12 is covered by a cover 14. The lid 14 has a lid top layer 16 and a lid bottom layer 18. A space is formed between the cover top layer 16 and the cover bottom layer 18 of the cover 14. The top cover layer 16 is provided with a hollow connection port 22 and the bottom cover layer 18 is provided with a hollow extension tube 24. Each extension tube 24 of the cover bottom layer 18 is inserted into a fluid sample 26 in each receptacle 20 of the porous disc 12.
An air passage is formed through the hollow connection port 22 of the cover top layer 16, the space between the cover top layer 16 and the cover bottom layer 18, and the hollow extension tube 24 of the cover bottom layer 18. When gas is injected from the connection port 22 of the top cover layer 16, the gas passes through the connection port 22 of the top cover layer 16, the space between the top cover layer 16 and the bottom cover layer 18, and the extension tube 24 of the bottom cover layer 18, applying pressure to the fluid sample 26 in the extension tube 24, thereby causing the level of the cell suspension in the extension tube 24 to drop. When a vacuum is drawn through the connection port 22 of the top cover layer 16, gas is drawn through the connection port 22 of the top cover layer 16, the space between the top cover layer 16 and the bottom cover layer 18, and the extension tube 24 of the bottom cover layer 18, thereby reducing the pressure applied to the fluid sample 26 in the extension tube 24, so that the liquid level of the fluid sample 26 in the extension tube 24 rises (as shown in fig. 1 (B)).
Fig. 2 is a system schematic diagram of a fluid control device 80 according to a first embodiment of the present invention. In the first embodiment, the fluid control device 80 includes the control unit 1 and four processing devices 30. It should be appreciated that fluid control device 80 may include more or less than four processing devices 30. Each of the processing devices 30 has the same structure and components, and thus only one processing device 30 will be described below. The fluid control device 80 includes the processing device 4 shown in fig. 1 (a) and (B). The processing device 4 is disposed in the chamber 32 of the processing device 30. In this case, the fluid control device 80 is associated with a bioreactor. In particular, the fluid control device 80 may include four processing devices 4, wherein each processing device 4 is disposed in a chamber 32 of the processing device 30, respectively.
In alternative embodiments, a processing device 4 may be used that does not include a fluid sample containing biological particles, but only includes chemical reagents. Alternatively, the processing device 4 may be a microfluidic device, in particular a microfluidic chip.
The control unit 1 comprises one pressure unit 2 and four connection units 8. The connection units 8 have the same structure and components, and thus only one connection unit 8 will be described below. It should be appreciated that the control unit 1 may comprise more or less than four connection units 8. In particular, the number of connection units 8 may correspond to the number of processing means 30.
In addition, the control unit 1 includes several sub-controllers, namely, a first sub-controller named as the pressure controller 41, a second sub-controller named as the flow controller 38, a third sub-controller named as the mixed gas controller 65, a fourth sub-controller named as the humidity controller 69, a fifth sub-controller named as the pressure controller 51, and a sixth sub-controller named as the vacuum controller 53. The flow controller 38, the pressure controller 41, the pressure controller 51, the vacuum controller 53, the mixed gas controller 65, and the humidity controller 69 may be integrated as one controller or a plurality of controllers.
The treatment device 30 includes a chamber 32 surrounded by a housing 76 of the treatment device 30. A humidifier 66 is disposed within the chamber 32. A processing device as shown in fig. 1 (a) and (B) is also provided within the chamber 32. The processing device 30 is mechanically connected to the control unit 1, in particular to the housing 77 of the control unit 1. In addition, the processing device 4 is in fluid connection with the first control unit outlet 3 and the processing device 30 is in fluid connection with the second control unit outlet 7. The first control unit outlet 3 is part of a pipe 78 of the control unit 1 and the second control unit outlet 7 is part of another pipe 79 of the control unit 1.
The pressure unit 2 comprises a pressurized gas tank 42 and a pump 46. The pump 46 pumps pressurized gas into the gas tank 42. A filter 54 is disposed downstream of the pump 46. Filter 54 filters out impurities in the gas pumped by pump 46 into pressurized gas tank 42. The pressure unit 2 further comprises a pressure controller 51 for controlling the pump 46, and a pressure gauge 50. The pressure gauge 50 measures the pressure of the positive pressure gas in the pressurized gas tank 42 to generate a positive pressure measurement signal. The pressure controller 51 receives the positive pressure measurement signal generated by the pressure gauge 50 and determines whether the positive pressure measurement signal is below a critical positive pressure value. If the positive pressure measurement signal is below the critical positive pressure value, then pressure controller 51 controls pump 46 to pump pressurized gas into pressurized gas tank 42; otherwise, the pump 46 does not pump gas into the pressurized gas tank 42.
The gas mixer 60 is disposed upstream of the pump 46. The gas mixer 60 mixes a plurality of types of gases, such as air (atmospheric air in this embodiment) and a specific mixed gas (carbon dioxide in this embodiment), supplied from a gas supply (not shown in the drawing), into a mixed gas having a preset concentration of the mixed gas (i.e., carbon dioxide having a preset concentration). The mixed gas is pressurized by a pump 46 to be pumped into the pressurized gas tank 42. The gas mixer 60 comprises two inlets 10 for gas entry and one outlet 9 for discharging the mixed gas.
The pressure unit 2 comprises a vacuum gas box 44 and a further pump 48. Another pump 48 evacuates the vacuum air box 44. A vacuum filter 56 is provided downstream of the vacuum tank 44 and filters out impurities in the gas in the vacuum tank 44 that is evacuated by the other pump 48.
In addition, the pressure unit 2 includes a vacuum gauge 52. The vacuum gauge 52 measures the pressure of the negative pressure gas in the vacuum gas tank 44 to generate a negative pressure measurement signal. The vacuum controller 53 receives the negative pressure measurement signal generated by the vacuum gauge 52 and determines whether the negative pressure measurement signal is greater than a critical negative pressure value. If the negative pressure measurement signal is greater than the critical negative pressure value, the vacuum controller 53 controls the other pump 48 to evacuate the vacuum air tank 44; otherwise, the other pump 48 does not evacuate the vacuum air box 44.
The connection unit 8 comprises a valve 34. The valve 34 is in fluid connection with a pipe 78 comprising the first control unit outlet 3. In addition, valve 34 is fluidly connected to vacuum tank 44 and pressurized tank 42. Pressurized gas tank 42 provides positive pressure gas to valve 34 and vacuum gas tank 44 provides negative pressure gas to valve 34. The check valve 58 of the pressure unit 2 is provided and arranged so that it can prevent the positive pressure gas provided by the pressurized gas tank 42 from flowing back to the valve 34.
The valve 34 delivers positive pressure gas and negative pressure gas alternately to the first control unit outlet 3 and thereby to the processing device 4. In particular, positive or negative pressure gas is delivered to the interior space of the lid 14 (i.e., the space between the lid top layer 16 and the lid bottom layer 18). This results in positive and negative pressure gases being applied to the fluid sample 26 in each extension tube 24 of the cap 14, thereby creating a liquid mixing mechanism that repeatedly pumps the fluid sample 26 up and down in each container 20 of the porous disc 12.
The flow sensor 36 of the connection unit 8 may be arranged downstream of the valve 34 and upstream of the first control unit outlet 3. The flow sensor 36 senses the gas flow rates of the positive pressure gas and the negative pressure gas delivered by the valve 34 into the processing device 4 (particularly the interior space of the lid 14 within the chamber 32), and generates a flow sensing signal. The flow controller 38 receives the flow sensing signal generated by the flow sensor 36 and determines a difference between the flow sensing signal and the target flow signal to control the opening of the valve 34, i.e., to control the gas flows of the positive pressure gas and the negative pressure gas delivered by the valve 34 into the processing apparatus 4 (particularly the interior space of the lid 14 within the chamber 32).
The connection unit 8 comprises a pressure sensor 40. The pressure sensor 40 senses the pressure in the chamber 32 of the processing device 30. In addition, the pressure sensor 20 senses the pressure in the inner space of the cover 14. Based on the sensed pressure signal, the pressure sensor 40 generates a pressure sensing signal. The pressure controller 41 of the control unit 1 receives the pressure sensing signal generated by the pressure sensor 40 and determines whether the pressure sensing signal is greater than or equal to a critical positive pressure value or lower than a critical negative pressure value to control the valve 34 to be connected to the passage, that is, when the pressure sensing signal of the cover 14 is greater than or equal to the critical positive pressure value, the pressure controller 41 controls the valve 34 to be connected to the passage of negative pressure gas (the passage connecting the vacuum tank 44); and when the pressure sensing signal is lower than or equal to the critical negative pressure value, the pressure controller 41 controls the valve 34 to be connected to the passage of the positive pressure gas (the passage connecting the pressurized gas tank 42).
The connection unit 8 further comprises a further valve 62 fluidly connected to the pressurized gas tank 42 for delivering the mixed gas in the pressurized gas tank 42 into the chamber 32 of the treatment device 30. Valve 62 is not fluidly connected to vacuum plenum 44. The connection unit 8 includes a mixed gas sensor 64 for sensing the concentration of the mixed gas in the chamber 32 and generating a mixed gas sensing signal.
The mixed gas controller 65 receives the mixed gas sensing signal generated by the mixed gas sensor 64 and determines whether the mixed gas sensing signal is greater than or equal to a mixed gas preset concentration value to control the opening or closing of the other valve 62. In addition, the mixed gas controller 65 controls the gas mixer 60 to mix air with a specific mixed gas into a mixed gas having a preset concentration of the mixed gas. This means that when the mixed gas sensing signal is greater than or equal to the mixed gas preset concentration value, the mixed gas controller 65 controls the other valve 62 to be closed, and when the mixed gas sensing signal is lower than the mixed gas preset concentration value, the mixed gas controller 65 controls the other valve 62 to be connected to the pressurized gas tank 42, and controls the gas mixer 60 to mix the plurality of types of gases supplied from the gas supply into the mixed gas having the mixed gas preset concentration.
The humidifier 66 is provided with a heater 70. The heater 70 heats the water in the humidifier 66 to increase the humidity in the chamber 32. The humidity sensor 68 of the connection unit 8 senses the humidity in the chamber 32 to generate a humidity sensing signal.
The humidity controller 69 receives the humidity sensing signal generated by the humidity sensor 68 and determines whether the humidity sensing signal is below a preset critical humidity value to control the heater 70 of the humidifier 66 for heating. This means that the humidity controller 69 controls the heater 70 of the humidifier 66 to heat the water in the humidifier 66 to increase the humidity in the chamber 32 when the humidity sensing signal is below a preset critical humidity value, and the humidity controller 69 controls the heater 70 of the humidifier 66 not to heat when the humidity sensing signal is greater than or equal to the preset critical humidity value.
The control unit 1 comprises a pressure unit 2 and a connection unit 8. The control unit 1 is adapted to process a liquid sample in the processing device 4 by applying a positive or negative pressure to the first control unit outlet 3 via a connection unit 8 in fluid connection with the pressure unit 2. In particular, the valve 34 is in fluid connection with the pressure unit 2. In addition, the control unit 1 is adapted to control the physical state in the chamber 32 of the processing device 30. In response, the other valve 65 and/or humidifier 66 are controlled. In particular, the control unit 1 is adapted to control the valve 65 such that the pressure unit 2 is fluidly connected or disconnected from the second control unit outlet 7.
As seen in fig. 2, the control unit 1 comprises a plurality of tubes 91. The tube 91 fluidly connects the components of the pressure unit 2 with the components of the connection unit 8. The fluid control device 80 shown in fig. 2 includes four processing devices 30. Thus, the tube 91 has four branches leading to the respective connection units 8. Tube branches are numbered with numbers placed in black circles.
The gas mixer 60 is connected to the gas mixing controllers 65 of the respective connection units 8 through electric wires 93. The wires are also branches, with each branch numbered and placed in a black circle.
Fig. 3 is a flow chart of the manner of operation of the fluid control device 80 according to the first embodiment of the present invention. The flow of steps in fig. 3 will be described with reference to the apparatus and system in fig. 1 (a), 1 (B) and 2.
In a first embodiment, a fluid sample 26 is injected into each receptacle 20 of the porous disc 12. The porous disc 12 is covered with the cap 14 such that each extension tube 24 of the cap 14 is inserted into the fluid 26 in each receptacle 20 of the porous disc 12. The porous plate 12 and the cover 14 are disposed in the chamber 32 of the processing apparatus (step S100).
The gas mixer 60 mixes a plurality of types of gases supplied from a gas supply, such as air (atmospheric air in this embodiment) and a specific mixed gas (carbon dioxide in this embodiment), into a mixed gas having a preset concentration of the mixed gas (i.e., carbon dioxide in this embodiment). The pump 46 pressurizes the mixed gas mixed by the gas mixer 60 into positive pressure gas to be pumped into the pressurized gas tank 42. The pressurized gas tank 42 connected to the valve 34 supplies positive pressure gas to the valve 34 (step S102).
The filter 54 filters out impurities in the mixed gas pumped by the pump 46 into the pressurized gas tank 42. Check valve 58 prevents the positive pressure gas provided by pressurized gas tank 42 from flowing back to valve 34. The pressure gauge 50 measures the pressure of the positive pressure gas in the pressurized gas tank 42 to generate a positive pressure measurement signal. The pressure controller 51 receives the positive pressure measurement signal generated by the pressure gauge 50 and determines whether the positive pressure measurement signal is below a critical positive pressure value. If the positive pressure measurement signal is below the critical positive pressure value, the pressure controller 51 controls the pressure pump 46 to pump the pressurized positive pressure gas into the pressurized gas tank 42; otherwise, the pump 46 does not pump gas into the pressurized gas tank 42.
The pump 48 evacuates the vacuum air tank 44 to make the air in the vacuum air tank 44 negative pressure air. The vacuum tank 44 connected to the valve 34 supplies negative pressure gas to the valve 34 (step S104).
The vacuum filter 56 filters out impurities in the negative pressure gas in the vacuum gas tank 44 that is evacuated by the vacuum pump 48. The vacuum gauge 52 measures the pressure of the negative pressure gas in the vacuum gas tank 44 to generate a negative pressure measurement signal. The vacuum controller 53 receives the negative pressure measurement signal generated by the vacuum gauge 52 and determines whether the negative pressure measurement signal is greater than a critical negative pressure value. If the negative pressure measurement signal is greater than the critical negative pressure value, the vacuum controller 53 controls the vacuum pump 48 to evacuate the vacuum air tank 44; otherwise, the vacuum pump 48 does not evacuate the vacuum air box 44.
The valve 34 is connected to a channel including a tube 91 and to which a pressurized gas tank 42 containing a positive pressure gas is connected, and the valve 34 delivers the positive pressure gas in the pressurized gas tank 42 via the first control unit outlet 3 to the processing device 4 within the chamber 32, in particular into the interior space of the valve cover 14, so that the positive pressure gas applies a positive pressure to the fluid sample 26 in each extension tube 24 of the cover 14.
The flow sensor 36 senses the gas flow of the positive pressure gas delivered by the valve 34 into the processing device 4 via the first control unit outlet 3 and generates a flow sensing signal. The flow controller 38 receives the flow sensing signal generated by the flow sensor 36 and determines the difference between the flow sensing signal and the target flow signal, and the flow controller 38 controls the opening degree of the valve 34 according to the difference (step S106).
The pressure sensor 40 senses the positive pressure of the positive pressure gas in the chamber 32 and in the inner space of the cover 14 within the chamber 32 and generates a positive pressure sensing signal. The pressure controller 41 receives the positive pressure sensing signal generated by the pressure sensor 40 and determines whether the positive pressure sensing signal is greater than or equal to a critical positive pressure value. If the positive pressure sensing signal is greater than or equal to the critical positive pressure value, the pressure controller 41 controls the valve 34 to be connected to the passage including the pipe 91 and connected to the vacuum tank 44 in which the negative pressure gas is stored (step S108).
The valve 34 is connected to a channel to which a vacuum gas tank 44 having negative pressure gas stored therein is connected, and the valve 34 delivers the negative pressure gas in the vacuum gas tank 44 into the inner space of the cover 14 within the chamber 32, thereby applying negative pressure to the fluid sample 26 in each extension tube 24 of the cover 14.
The flow sensor 36 senses the gas flow of the negative pressure gas delivered by the valve 34 into the interior space of the lid 14 within the incubation chamber 32 and generates a flow sensing signal. The flow controller 38 receives the flow sensing signal generated by the flow sensor 36 and determines the difference between the flow sensing signal and the target flow signal, and the flow controller 38 controls the opening degree of the valve 34 according to the difference (step S110).
The pressure sensor 40 senses the negative pressure of the negative pressure gas in the chamber 32 and the inner space of the cover 14 within the chamber 32 and generates a negative pressure sensing signal. The pressure controller 41 receives the negative pressure sensing signal generated by the pressure sensor 40 and determines whether the negative pressure sensing signal is lower than or equal to a critical negative pressure value. If the negative pressure sensing signal is lower than or equal to the critical negative pressure value, the pressure controller 41 controls the valve 34 to be connected to the passage connecting the pressurized gas tank 42 in which the positive pressure gas is stored (step S112).
Steps S106, S108, S110 and S112 are repeated to generate positive and negative pressure gases that flow into the chamber 32 through the valve 34 and the first control unit outlet 3 to apply positive and negative pressures to the fluid sample 26 in each extension tube 24 of the cap 14, thereby creating a liquid mixing mechanism that repeatedly pumps the fluid sample 26 up and down in each container 20 of the porous disc 12.
Another valve 62 connected to the pressurized gas tank 42 delivers the mixed gas in the pressurized gas tank 42 into the chamber 32 via a second control unit outlet. The mixed gas sensor 64 senses the concentration of the mixed gas in the incubation chamber 32 and generates a mixed gas sensing signal.
The mixed gas controller 65 receives the mixed gas sensing signal generated by the mixed gas sensor 64 and determines whether the mixed gas sensing signal is greater than or equal to a mixed gas preset concentration value to control the opening or closing of the other valve 62 and control the gas mixer 60 to mix air and a specific mixed gas into a mixed gas having a mixed gas preset concentration. This means that when the mixed gas sensing signal is greater than or equal to the mixed gas preset concentration value, the mixed gas controller 65 controls the other valve 62 to be closed, and when the mixed gas sensing signal is lower than the mixed gas preset concentration value, the mixed gas controller 65 controls the valve 62 to be connected to the pressurized gas tank 42 and controls the gas mixer 60 to mix the plurality of types of gases supplied from the gas supplier into the mixed gas having the mixed gas preset concentration (step S114).
A humidifier 66 is disposed within the chamber 32. The humidifier 66 is provided with a heater 70. The heater 70 heats the water in the humidifier 66 to increase the humidity in the chamber 32. The humidity sensor 68 senses the humidity in the incubation chamber 32 to generate a humidity sensing signal.
The humidity controller 69 receives the humidity sensing signal generated by the humidity sensor 68 and determines whether the humidity sensing signal is lower than a preset critical humidity value to control the heater 70 of the humidifier 66 to heat, i.e., if the humidity sensing signal is lower than the preset critical humidity value, the humidity controller 69 controls the heater 70 of the humidifier 66 to heat the water in the humidifier 66 to increase the humidity in the incubation chamber 32, and if the humidity sensing signal is greater than or equal to the preset critical humidity value, the humidity controller 69 controls the heater 70 of the humidifier 66 not to heat (step S116).
Fig. 4 is a system schematic diagram of a fluid control device 80 according to a second embodiment of the present invention. The difference between the system configuration of the fluid control device 80 in the second embodiment and the system configuration of the fluid control device 80 in the first embodiment is that the fluid control device 80 in the second embodiment is provided with an acquisition unit (such as an optical imaging apparatus 82 provided on a movable electronic platform for scanning) or is provided with four optical imaging apparatuses 82. The remaining devices in the fluid control device 80 in the second embodiment are the same as those in the fluid control device 80 in the first embodiment and use the same reference numerals. For simplicity of explanation, the following description will be made using one optical imaging device 82 in each incubation chamber 32. The same operations and functions apply to the rest of the devices.
The optical imaging device 82 optically tests the liquid pH and the amount of liquid dissolved oxygen of the fluid sample 26 in the container 20 of the porous disc 12 of the incubation chamber 32. The mixed gas controller 65 receives the liquid pH value and the liquid dissolved oxygen amount tested by the optical imaging apparatus 82 and determines whether the liquid pH value is greater than the critical liquid pH value and whether the liquid dissolved oxygen amount is less than the critical liquid dissolved oxygen amount to control the opening or closing of the other valve 62, and controls the gas mixer 60 to mix the plurality of types of gas supplied from the gas supplier into the mixed gas having the preset liquid pH value and the preset liquid dissolved oxygen amount, that is, when the test liquid pH value is less than or equal to the critical liquid pH value and the liquid dissolved oxygen amount is greater than or equal to the critical liquid dissolved oxygen amount, the mixed gas controller 65 controls the other valve 62 to be closed; when the test liquid pH is greater than the critical liquid pH and the liquid dissolved oxygen is less than the critical liquid dissolved oxygen, the mixed gas controller 65 controls the valve 62 to be connected to the pressurized gas tank 42 and controls the gas mixer 60 to mix the plurality of types of gases provided by the gas supplier into a mixed gas having a preset liquid pH and a preset liquid dissolved oxygen.
Fig. 5 is a flowchart of an operation mode of cultivating cells or microorganisms in a fluid control device according to a second embodiment of the present invention. The flow of steps in fig. 5 is described with reference to the apparatus and system of fig. 1 (a), 1 (B) and 4.
The functional operations of the flow steps S100, S102, S104, S106, S108, S110, S112, S114, and S116 in the second embodiment are the same as those of the flow steps S100, S102, S104, S106, S108, S110, S112, S114, and S116 in the first embodiment, and thus the description thereof is omitted here. The difference is that the functional operation of step S118 of controlling the liquid pH and the amount of liquid dissolved oxygen of the cell suspension is added in the second embodiment.
The optical imaging apparatus 82 optically tests the liquid pH and the amount of liquid dissolved oxygen of the fluid sample 26 in the container 20 of the porous disc 12 of the chamber 32. The mixed gas controller 65 receives the liquid pH value and the liquid dissolved oxygen amount tested by the optical imaging apparatus 82 and determines whether the liquid pH value is greater than a critical liquid pH value and whether the liquid dissolved oxygen amount is lower than the critical liquid dissolved oxygen amount to control the opening or closing of the other valve 62 and control the gas mixer 60 to mix the plurality of types of gas supplied from the gas supplier into the mixed gas having the preset liquid pH value and the preset liquid dissolved oxygen amount, that is, when the test liquid pH value is lower than or equal to the critical liquid pH value and the liquid dissolved oxygen amount is greater than or equal to the critical liquid dissolved oxygen amount, the mixed gas controller 65 controls the other valve 62 to be closed; when the test liquid pH is greater than the critical liquid pH and the liquid dissolved oxygen is less than the critical liquid dissolved oxygen, the mixed gas controller 65 controls the other valve 62 to be connected to the pressurized gas tank 42 and controls the gas mixer 60 to mix the plurality of types of gases provided by the gas supplier into a mixed gas having a preset liquid pH and a preset liquid dissolved oxygen (step S118).
Fig. 6 is a system schematic diagram of a fluid control device 80 according to a third embodiment of the present invention. The difference between the system structure of the fluid control device 80 in the third embodiment and the system structure of the fluid control device 80 in the first embodiment is that the fluid control device 80 in the third embodiment is provided with four additional heating units. Each of the heating units includes a heating plate 92, a thermal block 94, a plurality of temperature sensors 96, and a temperature controller 98. The remaining devices in the fluid control device 80 in the third embodiment are the same as those of the fluid control device 80 in the first embodiment and use the same reference numerals. For simplicity of explanation, one heating plate 92, one thermal block 94, and one temperature controller 98 are used in each incubation chamber 32. The same operations and functions apply to the rest of the devices.
A thermal block 94 is disposed in the chamber 32. The porous disc 12 is disposed on a thermal block 94. A heating plate 92 is disposed in the chamber 32. A thermal block 94 is disposed on the heating plate 92. The heating plate 92 heats the thermal block 94 such that the thermal block 94 indirectly heats the porous disc 12.
A plurality of temperature sensors 96 located between the thermal block 94 and the porous disk 12 sense a plurality of heating temperature values of the heating performed by the thermal block 94 on the porous disk 12. The temperature controller 98 receives the plurality of heating temperature values generated by the plurality of temperature sensors 96 and determines whether the plurality of heating temperature values are lower than a preset critical temperature value to control the heating plate 92 to heat the thermal block 94, i.e., if the plurality of heating temperature values are lower than the preset critical temperature value, the temperature controller 98 controls the heating plate 92 to heat the thermal block 94 such that the thermal block 94 indirectly heats the porous disc 12; and if the plurality of temperature sensing signals are all greater than or equal to the preset critical temperature value, the temperature controller 98 controls the heating plate 92 not to heat the thermal block 94.
FIG. 7 is a flow chart of the operation of incubating cells in a fluid control device according to a third embodiment of the present invention. The flow of steps in fig. 7 is described with reference to the apparatus and system of fig. 1 (a), 1 (B) and 6.
The functional operations of the flow steps S100, S102, S104, S106, S108, S110, S112, S114, and S116 in the third embodiment are the same as those in the flow steps S100, S102, S104, S106, S108, S110, S112, S114, and S116 in the first embodiment, and thus the description thereof is omitted here. The difference is the functional operation of step S120 of controlling the liquid temperature of the cell suspension is added in the third embodiment.
The porous disc 12 is disposed on a thermal block 94 disposed in the chamber 32. A thermal block 94 is disposed on a heating plate 92 disposed in the chamber 32. The heating plate 92 heats the thermal block 94 such that the thermal block 94 indirectly heats the porous disc 12.
A plurality of temperature sensors 96 located between the thermal block 94 and the porous disc 12 sense a plurality of heating temperature values of the heating of the porous disc 12 by the thermal block 94. The temperature controller 98 receives the plurality of heating temperature values generated by the plurality of temperature sensors 96 and determines whether the plurality of heating temperature values are lower than a preset critical temperature value to control the heating plate 92 to heat the thermal block 94, i.e., if the plurality of heating temperature values are lower than the preset critical temperature value, the temperature controller 98 controls the heating plate 92 to heat the thermal block 94 such that the thermal block 94 indirectly heats the porous disc 12; and if the plurality of temperature sensing signals are all greater than or equal to the preset critical temperature value, the temperature controller 98 controls the heating plate 92 not to heat the thermal block 94 (step S120).
Fig. 8 shows a perspective view of the treatment device 30. In particular, the side of the processing device 30 in contact with the control unit 1 is shown. The treatment device 30 may be used in each of the aforementioned fluid control devices 80 and comprises a fluid connector 71 for fluidly connecting the tube 78 of the control unit 1 with the processing device 4. The fluid connector 71 protrudes from the side of the treatment device 30 and includes a hollow portion. The tube 78 of the control unit 1 is inserted into the hollow portion of the fluid connector 71. In addition, the treatment device 30 includes another fluid connector 72. The further fluid connector 72 is used to fluidly connect a further tube 79 of the control unit 1 with the chamber 32 of the treatment device 30. The treatment device 30 further comprises an additional fluid connector 95. The additional fluid connector 95 is used to connect the pressure sensor 40 with the processing device 4 and the chamber 32. Another additional fluid connector 72, 95 protrudes from the side of the treatment device 30 as does the fluid connector 71.
The processing means 30 comprises a connection area 97 for mechanically connecting the processing means 30 with the control unit 1. In particular, the connection region 97 may have a through-hole for receiving a connection member (e.g., a screw) by which the two components are mechanically connected.
Fig. 9 is a perspective view of a part of the control unit 1. Fig. 9 does not show all the aforementioned components of the control unit 1. In particular, fig. 9 does not show the upper part of the covering control unit 1, the pipe and fluid connections between the control unit 1 and the treatment device 30 and the processing device 4 are not shown. The aforementioned fluid control device 80 may comprise a control unit 1 as shown in fig. 9.
Fig. 9 shows that the control unit 1 has a housing 77 surrounding the interior space in which the pressure unit 2 and the connection unit 8 are arranged. When the processing device 30 is in fluid and mechanical connection with the control unit 1, the housing 77 is in direct contact with the housing 76 of the processing device 30. The control unit 1 comprises receiving portions 35 for receiving the processing modules 30, respectively. In particular, the control unit 1 comprises four receiving portions 35 for receiving one processing module 30 each.
Fig. 10 shows a perspective view of the fluid control device 80. The fluid control device 80 may be one of the fluid control devices described previously. The fluid control device 80 comprises a control unit 1, in particular a control unit 1 as shown in fig. 9, and a plurality of processing devices 30 in fluid and mechanical connection with the control unit 1. The treatment devices 30 are disposed adjacent to each other along the length axis of the fluid control device 80. In addition, each processing means 30 is arranged in one receiving portion 35 of the control unit 1.
Description of the reference numerals
1 control unit
2 pressure unit
3 first control unit outlet
4 processing device
5 biological particles
6 liquid
7 second control unit outlet
8 connecting unit
9 outlet port
10 inlet port
12 porous plate
14 cover
16 cover top layer
18 cover bottom layer
20 Container
22 connection port
24 extension tube
26 fluid sample
30 processing apparatus
32 chamber(s)
34 valve
35 receiving part
36 flow sensor
38 flow controller
40 pressure sensor
41 pressure controller
42 pressurized gas tank
44 vacuum air box
46 pump
48 another pump
50 pressure gauge
51 pressure controller
52 vacuum gauge
53 vacuum controller
54 filter
56 another gas filter
58 check valve
60 gas mixer
62 another valve
64 Mixed gas sensor
65 mixed gas controller
66 humidifier
68 humidity sensor
69 humidity controller
70 heater
71 fluid connector
72 another fluid connector
76 housing of the treatment device
77 housing of control unit
78 tube
79 another pipe
80 fluid control device
82 optical imaging apparatus
91 tube
92 heating plate
93 electric wire
94 thermal block
95 additional fluid connector
96 temperature sensor
97 connecting region
98 temperature controller

Claims (31)

1. A control unit (1) for a fluid control device (80), wherein the control unit (1) comprises:
A pressure unit (2) for providing a positive and/or negative pressure,
at least one first control unit outlet (3) which is fluidly connectable to a processing device (4) comprising at least one container (20) for receiving a fluid sample (26) (5),
at least one second control unit outlet (7) fluidly connectable to a processing device (30) having a chamber (32) for receiving the processing device (4), and
-a connection unit (8) by means of which the pressure unit (2) is fluidly connectable or fluidly connected to the first control unit outlet (3) and/or the second control unit outlet (7), wherein
The control unit (1) is adapted to control the processing of the fluid sample (26) in the processing device (4) by applying positive or negative pressure provided by the pressure unit (2) to the first control unit outlet (3) by the connection unit (8) and to control a physical state in the chamber (32) of the processing device (4).
2. The control unit (1) according to claim 1, characterized in that the control unit (1) is adapted to control a physical state in the chamber (32) of the processing device by fluidly connecting or disconnecting the pressure unit (2) with the second control unit outlet (7) by means of the connection unit (8).
3. The control unit (1) according to claim 1 or 2, characterized in that the pressure unit (2) comprises a pressurized gas tank (42) with a positive pressure, wherein the pressurized gas tank (42) is fluidly connectable or fluidly connected to the first control unit outlet (3) and/or the second control unit outlet (7).
4. A control unit (1) according to any one of claims 1 to 3, characterized in that the pressure unit comprises a vacuum gas tank (44) with a negative pressure, wherein the vacuum gas tank (44) is fluidly connectable or fluidly connected to the first control unit outlet (3) and/or the second control unit outlet (7).
5. The control unit (1) according to any one of claims 1 to 4, characterized in that the pressure unit (2) comprises a gas mixer (60) which
a. Arranged upstream and/or in the pressurized gas tank (42)
b. Comprising at least two inlets (10) and/or at least two inlets for gas entry
c. Comprising an outlet (9) for releasing the mixed gas.
6. The control unit (1) according to any one of claims 3 to 5, characterized in that the pressure unit (2) comprises
a. A pump (46) arranged upstream of the pressurized gas tank (42) and/or adapted to increase the pressure in the pressurized gas tank (42), and/or
b. A gas filter (54) disposed upstream of the pressurized gas tank (42) for filtering gas.
7. The control unit (1) according to any one of claims 3 to 6, characterized in that the pressure unit (2) comprises
a. A further pump (48) arranged downstream of the vacuum gas tank (44) and/or adapted to reduce the pressure in the vacuum gas tank (44), and/or
b. And a further gas filter (56) provided downstream of the vacuum gas tank (44).
8. The control unit (1) according to any one of claims 1 to 7, characterized in that the pressure unit (2) comprises a check valve (58), the check valve (58) being fluidly arranged between the pressurized gas tank (42) and the first control unit outlet (3) and/or the second control unit outlet (7).
9. The control unit (1) according to any one of claims 1 to 8, characterized in that,
a. the control unit (2) is adapted to supply the same gas to the treatment device (30) and the processing device (4), and/or
b. The pressurized gas tank (42) supplies the same gas to the first control unit outlet (3) and the second control unit outlet (7).
10. The control unit (1) according to any one of claims 3 to 9, characterized in that the connection unit comprises at least one valve (34) for selectively fluidly connecting the pressurized air tank (42) or the vacuum air tank (44) with the first control unit outlet (3).
11. The control unit (1) according to any one of claims 3 to 10, characterized in that the connection unit (8) comprises at least one further valve (62) which in a first position fluidly connects the pressurized gas tank (42) with the processing device (30) and in a second position decouples the fluid connection between the pressurized gas tank (42) and the processing device (30).
12. The control unit (1) according to claim 10 or 11, characterized in that the control unit (1) comprises at least one controller for controlling the valve (34) and/or the further valve (62).
13. The control unit (1) according to claim 12, characterized in that,
a. the controller controls the valve (34) based on the gas flow through the first control unit outlet (3), and/or
b. The controller controls the valve (34) based on a physical state, in particular pressure, in the processing device (30) and based on a physical state, in particular pressure, of the processing device (4).
14. The control unit (1) according to any one of claims 10 to 13, characterized in that,
a. the controller controls the opening of the outlet of the valve (34) based on the gas flow through the first control unit outlet (9), and/or
b. The controller controls whether the valve (34) fluidly connects the first control unit outlet (3) with the pressurized gas tank (42) or with the vacuum gas tank (44) based on the physical state of the processing device (30) and based on the physical state of the processing device.
15. The control unit (1) according to any one of claims 12 to 14, characterized in that,
a. the controller controls the further valve (62) based on a physical state of the chamber (32) of the processing device (30), in particular a gas composition, and/or a physical state of the fluid sample (26) located in the processing device (4), and/or
b. The controller controls the gas mixer (60) based on a physical state of the chamber (32) of the processing device (30), in particular a gas composition, and/or a physical state of the fluid sample (26) located in the processing device (4).
16. The control unit (1) according to any one of claims 12 to 15, characterized in that,
a. the controller is adapted to control a humidifier (66) disposed in the chamber of the treatment device (30), or
b. The controller is adapted to control a physical state in the chamber (32) of the processing device (30) by controlling a humidifier (66) disposed in the chamber (32).
17. The control unit (1) according to any one of claims 12 to 16, wherein the controller comprises:
a. a first sub-controller for controlling whether the valve (34) fluidly connects the first control unit outlet (3) with the pressurized gas tank (42) or with the vacuum gas tank (44), and/or
b. A second sub-controller for controlling the opening of the outlet opening of the valve (34), and/or
c. A third sub-controller for controlling the further valve (62) and/or the gas mixer (60), and/or
d. And a fourth sub-controller for controlling the humidifier.
18. The control unit (1) according to any one of claims 1 to 17, characterized in that it comprises a housing which is provided around an inner space of the pressurized gas tank (42) and/or the vacuum gas tank (44) and/or the pump (46) and/or the further pump (48) and/or the gas mixer (60) and/or the valve (32) and/or the further valve (62) and/or the check valve (58).
19. The control unit (1) according to claim 18, characterized in that,
a. the housing (77) has at least one through-hole for receiving a fluid connector (71) of the treatment device (30) and/or another through-hole for receiving another fluid connector (72) of the processing device (4), and/or
b. The housing (77) is mechanically connectable to the processing device (30).
20. The control unit (1) according to any one of claims 1 to 19, characterized in that it comprises:
a. a plurality of first control unit outlets (3), wherein each of the plurality of first control unit outlets (3) is fluidly connectable to one processing device (4), and/or
b. A plurality of second control unit outlets (7), wherein each of the plurality of second control unit outlets (7) is fluidly connectable to one processing device (30).
21. The control unit (1) according to claim 20, characterized in that,
a. the control unit (1) comprises only one pressure unit (2), and/or
b. The control unit (1) comprises several connection units (8), and/or
c. The pressurized gas tank (42) may be connected to or connected to each of the plurality of first control unit outlets (3) and/or each of the plurality of second control unit outlets (7), and/or
d. The vacuum air box (44) may be connected to or connected to each of the plurality of first control unit outlets (3).
22. The control unit (1) according to claim 20 or 21, characterized in that it comprises:
a. A plurality of valves (34), wherein each of the plurality of valves (34) is in fluid connection with one of the plurality of first control unit outlets (3) and the pressurized gas tank (42) and the vacuum gas tank (44), and/or
b. A plurality of valves (34), wherein each of the plurality of valves (34) is fluidly connected with one of the plurality of second control unit outlets (7) and the pressurized gas tank (42).
23. The control unit (1) according to any one of claims 1 to 22, characterized in that it comprises an acquisition unit, in particular an optical imaging device (82), for acquiring information about the fluid sample (26) in the processing device (4).
24. The control unit (1) according to claim 23, wherein the acquisition unit determines the physical state of the fluid sample (26) located in the processing device (4) based on the acquired information.
25. Fluid control device (80) comprising a control unit (1) according to any one of claims 1 to 24, at least one processing device (30) and at least one processing device (4) arranged in a chamber (32) of the processing device (30), wherein the processing device (4) is in fluid connection with the first control unit outlet (3) and the processing device (30) is in fluid connection with the second control unit outlet (7).
26. The fluid control device (80) of claim 25, wherein,
a. the processing device (4) comprises at least one container (20) for receiving the fluid sample (26) and a cover (14) covering the container (20), or
b. The processing device (4) comprises at least one container (20) for receiving the fluid sample (26) and a cover (14) covering the container (20), wherein the cover (14) comprises at least one extension tube (24) extending into the container (20) and being in fluid connection with the first control unit outlet (3).
27. The fluid control device (80) of claim 25 or 26, wherein the controller controls the valve (34) such that either a positive pressure provided by the pressurized gas tank (42) is applied to the container (20) via the lid (14) or a negative pressure provided by the vacuum gas tank (44) is applied to the container (20) via the lid (14).
28. The fluid control device (80) according to any one of claims 25 to 27, wherein the controller controls the further valve (62) such that a predetermined physical state is achieved in the chamber (32) of the processing device (30).
29. The fluid control device (80) according to any one of claims 25 to 28, wherein the processing device comprises a humidifier (66) controlled by a controller of the control unit (1).
30. The fluid control device (80) according to any one of claims 25 to 29, wherein,
a. the treatment device comprises a heating unit for heating the processing device (4) and/or the chamber (32) of the treatment device (30), and/or
b. The control unit (1) is adapted to control a physical state in the chamber (32) of the processing device (30) by controlling the heating unit.
31. The fluid control device (80) according to any one of claims 25 to 30,
a. the treatment device (30) comprises a housing (76) surrounding a chamber (32) in which the processing device (4) is arranged, and/or
b. The processing device (30) comprises a transparent housing portion enabling the acquisition unit to acquire information about a fluid sample (26) located in the processing device (4).
CN202180079176.9A 2020-12-03 2021-11-29 Control unit for a fluid control device Pending CN116547374A (en)

Applications Claiming Priority (3)

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LU102254A LU102254B1 (en) 2020-12-03 2020-12-03 Control unit for a fluid control device
LULU102254 2020-12-03
PCT/EP2021/083388 WO2022117509A1 (en) 2020-12-03 2021-11-29 Control unit for a fluid control device

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EP (1) EP4255628A1 (en)
JP (1) JP2023551838A (en)
CN (1) CN116547374A (en)
LU (1) LU102254B1 (en)
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WO (1) WO2022117509A1 (en)

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KR100809836B1 (en) * 2007-02-16 2008-03-04 고려대학교 산학협력단 An incubating apparatus with pressure controlled
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LU100171B1 (en) 2017-04-13 2018-10-15 Cytena Gmbh Device for processing a liquid sample
WO2018232096A1 (en) * 2017-06-14 2018-12-20 EMULATE, Inc. Effects of space travel on human brain cells
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LU102254B1 (en) 2022-06-03
TW202223573A (en) 2022-06-16
WO2022117509A1 (en) 2022-06-09
JP2023551838A (en) 2023-12-13
US20230415142A1 (en) 2023-12-28

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